This invention relates to certain benzo-fused heterocycles, namely benzothiophenes, benzofurans and indoles, which are substituted by a carboxy, lower alkoxycarbonyl or carbamoyl group. Such compounds are able to selectively inhibit the action of the thromboxane synthetase enzyme without significantly inhibiting the action of the prostacyclin synthetase or cyclooxygenase enzymes. The compounds are thus useful as therapeutic agents, for example, in the treatment of thrombosis, ischaemic heart disease, stroke, transient ischaemic attack, migraine and the vascular complications of diabetes.
European Pat. No. 3901, published Aug. 5, 1981, describes 3-(1-imidazol-1-ylalkyl)indoles in which the 2-position may be substituted with lower alkyl, lower cycloalkyl, adamantyl, phenyl or benzyl or substituted phenyl or benzyl groups. The compounds are reported as selective inhibitors of the thromboxane synthetase enzyme.
Other 3-(1-imidazol-1-ylalkyl)indoles useful as selective inhibitors of the thromboxane synthetase enzyme are reported in British Patent Application No. 2,045,244A, published Oct. 29, 1980. Said compounds may be substituted at the 2-position by alkyl, cycloalkyl phenyl or substituted phenyl, and are substituted at the 1-position by -X-Y wherein X is benzyl, furylmethyl, thienylmethyl or (C.sub.1-3)alkylene; and Y is carboxy, carbalkoxy, carbamyl, cyano, 5-tetrazolyl, amino, acylamino, sulfamyl or substituted derivatives thereof.
European Patent Application No. 3560, published Aug. 22, 1979, describes 1-skatolylimidazole [3-(1-imidazolylmethyl)indole] and 1-(1-methylindol-2-ylmethyl)imidazole[1-methyl-2-(1-imidazolylmethyl)indol e] as thromboxane synthetase inhibitors.
It has now been found that certain benzothiophenes, benzofurans and indoles in which the benzenoid ring is substituted by a 1-imidazolyl alkyl, a 2-(1-imidazolyl)ethoxy, a (3- or 4)-pyridylalkyl, pyridylvinyl, pyridyloxymethyl or pyridylmethoxy group are efficient inhibitors of the thromboxane synthetase enzyme.